Systemic autoimmune disorder is a disease that is classified as a form of primary immunodeficient syndrome, which is caused by a deficiency in the innate immune system (and especially a deficiency involving pattern-recognition receptors) and is characterized by exhibiting an uncontrollable immune response. Neonatal onset multisystem inflammatory disease (NOMID) is a disease belonging to a group of such systemic autoimmune disorders, and the NLRP3 gene has been identified as the cause of NOMID (Non-Patent Document 1). Clinical findings regarding NOMID include many pathological conditions characterized by neonatal onset chronic inflammation, urticarial rash, and epiphyseal hyperplasia of long bones (Non-Patent Document 2).
Regarding physiological functions of the NLRP3 gene, when the gene is activated by a ligand, a protein complex called “NLRP3 inflammasome” which comprises a plurality of proteins is formed to activate capase-1, cleave pro IL-1β, and eventually activate IL-1β (Non-Patent Documents 3 to 6). Previously attempted therapies for NOMID patients include an anti-IL-1β therapy targeting IL-1β. Although such therapy is effective in suppressing systemic inflammation, it is not sufficiently effective against pathological conditions such as epiphyseal hyperplasia of long bones (Non-Patent Document 7). Therefore, the development of a novel therapy from a different perspective regarding the pathological conditions of NOMID has been awaited.
Meanwhile, in the field of regenerative medicine or the like, technology for converting cells that are useful as biomaterial into cells of a desired cell type has been anticipated. Recently, mouse and human induced pluripotent stem cells (iPS cells) have been established. Yamanaka et al. succeeded in establishing iPS cells by introducing four genes (namely, Oct3/4, Sox2, Klf4, and c-Myc) into human-skin-derived fibroblasts (Patent Document 1 and Non-Patent Document 8). iPS cells that are obtained in the above manner are produced using cells from patients to be treated, thereby allowing them to differentiate into cells of an arbitrary organ. Therefore, iPS cells are considered to enable in vitro reproduction of pathological conditions. Hitherto, successful production of iPS cells from NOMID patients has been reported (Non-Patent Document 9). However, there have been no reports on successful in vitro reproduction of the pathological conditions of NOMID.